The University of Colorado Comprehensive Cancer Center (UCCC) is the only NCl-designated Cancer Center in Colorado serving a primary catchment area of Colorado and Wyoming with a population of ~5.5m. The mission of the UCCC is to discover, develop, and deliver breakthroughs in the diagnosis, treatment, and prevention of cancer with the underlying theme of personalized care woven throughout the enterprise. Structured as a matrix center within the Univ. of Colorado School of Medicine, the UCCC is an NCI-recognized consortium encompassing Univ. of Colorado Boulder, Colorado State University, National Jewish Health, Univ. of Colorado Hospital, the Children's Hospital, Denver Health System, Kaiser Permanente of Colorado and the Denver Veterans Administration Medical Center. The consortium institutions have made commitments to cancer medicine of approximately $101M since 2005. There are 248 full members (nearly all NIH funded cancer researchers in the state of Colorado) who participate in six research programs including: Cancer Cell Biology; Molecular Oncology; Developmental Therapeutics; Hormone-Related Malignancies; Lung, Head & Neck Cancer, and Cancer Prevention and Control. During the past five years, peer-reviewed cancer-related funding reached $102M and 3,181 publications (35% collaborative) were produced. Our innovation in research is exemplified by our members' lead roles in a lung cancer SPORE, LIVESTRONG Center of Excellence, biomarker development (ALK rearrangement, EGFR) for individualized therapy by our Pathology Shared Resource and development of a top Animal Cancer Center. Annual accrual to therapeutic trials increased from 595 to 1,044 which represent 27% of newly diagnosed patients. Research is supported by 13 Shared Resources located across the consortium and accessible to all UCCC members. These resources leverage NIH investments in our Colorado Clinical and Translational Science Institute (CCTSI) to provide cost efficiencies by avoiding duplication and enhancing critical mass. Development activities focused on strategic recruitments and pilot and seed grant programs have led to a return On investment of $11M in direct cancer research grant funding. During the next five years, our Strategic Plan includes development of programs in Metastasis and Tumor Microenvironment, Cancer Stem Cells, Survivorship and Health Disparities and a Human Research imaging Shared Resource which will cross species and enhance our drug development pipeline and personalized therapy clinical trials. Additional clinical and research facilities in construction, will allow us to maintain our upward research and clinical growth trajectory.